Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases, Aldo e Cele Daccò, Villa Camozzi, Ranica, Italy.
J Am Soc Nephrol. 2012 Aug;23(8):1416-25. doi: 10.1681/ASN.2012020181. Epub 2012 Jul 19.
Selective depletion of B cells with the mAb rituximab may benefit the autoimmune glomerular disease idiopathic membranous nephropathy (IMN). Here, we describe our experience treating 100 consecutive IMN patients with persistent nephrotic syndrome with rituximab. We defined complete remission as persistent proteinuria <0.3 g/24 h and partial remission as persistent proteinuria <3 g/24 h, each also having >50% reduction in proteinuria from baseline. During a median follow-up of 29 months after rituximab administration, 65 patients achieved complete or partial remission. The median time to remission was 7.1 months. All 24 patients who had at least 4 years of follow-up achieved complete or partial remission. Rates of remission were similar between patients with or without previous immunosuppressive treatment. Four patients died and four progressed to ESRD. Measured GFR increased by a mean 13.2 (SD 19.6) ml/min per 1.73 m(2) among those who achieved complete remission. Serum albumin significantly increased and albumin fractional clearance decreased among those achieving complete or partial remission. Proteinuria at baseline and the follow-up duration each independently predicted the decline of proteinuria. Furthermore, the magnitude of proteinuria reduction significantly correlated with slower GFR decline (P=0.0001). No treatment-related serious adverse events occurred. In summary, rituximab achieved disease remission and stabilized or improved renal function in a large cohort of high-risk patients with IMN.
用单抗利妥昔单抗选择性耗竭 B 细胞可能有益于自身免疫性肾小球疾病特发性膜性肾病(IMN)。在这里,我们描述了我们用利妥昔单抗治疗 100 例连续 IMN 患者持续性肾病综合征的经验。我们将完全缓解定义为持续蛋白尿<0.3 g/24 h,部分缓解定义为持续蛋白尿<3 g/24 h,且每种情况均较基线蛋白尿减少>50%。在利妥昔单抗给药后中位随访 29 个月期间,65 例患者达到完全或部分缓解。缓解的中位时间为 7.1 个月。所有 24 例至少随访 4 年的患者均达到完全或部分缓解。有或无既往免疫抑制治疗的患者缓解率相似。4 例患者死亡,4 例进展为 ESRD。完全缓解者的估计肾小球滤过率(eGFR)平均增加 13.2(SD 19.6)ml/min/1.73 m²。完全或部分缓解者血清白蛋白显著增加,白蛋白分数清除率降低。达到完全缓解或部分缓解的患者,其蛋白尿基线值和随访时间均独立预测蛋白尿下降。此外,蛋白尿减少的幅度与 GFR 下降速度显著相关(P=0.0001)。未发生与治疗相关的严重不良事件。总之,利妥昔单抗在一大群高危 IMN 患者中实现了疾病缓解,并稳定或改善了肾功能。